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Mol Nutr Food Res. 2017 Apr;61(4). doi: 10.1002/mnfr.201500960. Epub 2016 Dec 23.

Piperine inhibits ABCA1 degradation and promotes cholesterol efflux from THP-1-derived macrophages.

Author information

1
Department of Pharmacognosy, University of Vienna, Vienna, Austria.
2
Institute of Medical Chemistry, Center for Pathobiochemistry and Genetics, Medical University of Vienna, Vienna, Austria.
3
Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, Poland.

Abstract

SCOPE:

Increased macrophage cholesterol efflux (ChE) is considered to have anti-atherosclerotic effect counteracting cardiovascular disease. The principle pungent ingredient of the fruits of Piper nigrum, piperine, is identified in this study as a ChE inducer in THP-1-derived macrophages, and mechanisms underlying this effect are explored.

METHODS AND RESULTS:

Without affecting cell viability, piperine concentration-dependently enhances ChE in THP-1-derived macrophages from 25 to 100 μM. The expression level of the key cholesterol transporter protein ATP-binding cassette transporter A1 (ABCA1) is significantly upregulated by piperine, as revealed by western blot analyses. However, two other ChE-mediating transporter proteins, ATP-binding cassette transporter G1 (ABCG1) and scavenger receptor class B member 1 (SR-B1), remain unaffected. Piperine exerts no influence on ABCA1 mRNA levels, but significantly inhibits the degradation of ABCA1, as evident by an increased half-life of the protein in the presence of cycloheximide. Furthermore, it is found that piperine likely interferes with the calpain-mediated ABCA1 degradation pathway and exhibits significant inhibition of calpain activity.

CONCLUSION:

Our findings suggest that piperine promotes ChE in THP-1-derived macrophages by upregulation of ABCA1, which might be mediated by inhibition of calpain activity. This novel bioactivity makes the dietary constituent piperine a good candidate to be further explored for therapeutic or preventive applications in the context of atherosclerosis.

KEYWORDS:

ABCA1; Calpain; Cholesterol efflux; Macrophages; Piperine

PMID:
27862930
PMCID:
PMC5382977
DOI:
10.1002/mnfr.201500960
[Indexed for MEDLINE]
Free PMC Article

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